Adrenal Gland
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Transcript of Adrenal Gland
Adrenal Gland
Outer cortex: Steroid hormones o Outer zona glomerulosa: minerelocorticoid hormone
Aldosterone: the principal minerelocorticoid Controlled by renin-angiotensin system
renin released from juxtaglomerular cells of the Kidney
Reduced renal perfusion pressure
decreased circulating blood volume
sympathetic stimulation Renin-Angiotensin 1- Angiotensin 11-
stimulate zona glomerulosa Aldosterone increases tranepithelial transport
of sodium by Kidney Promotes secretion of potassium
o Inner zona faciculata and reticularis: Glucocorticoids, androgens, estrogens
Major glucocorticoid: Cortisol Under control of ACTH(pituitary) which in turn
is regulated by CRF (hypothalamus) Negative feedback control Pulsatile secretion with diurnal variation
Inner medulla: Catecholamines o Sympathetic system
Adrenal cortical hypofunction
Primary o Combined Minerelocorticoid and Glucocorticoid
deficiency o Isolated Aldosterone deficiency
Secondary
o Hypopituitarism No Minerelocorticoid deficiency (not regulated
by ACTH) Hyperpigmentation is absent co-existent thyroid and gonadal deficiency
o Exogenous glucocorticoids o Hyporeninemic hypoaldosteronism
Symptoms of Addisons disease o Anorexia and weight loss o Weakness o Apathy o Hypotension / Hypovolemia o Inability to withstand stress o Hyponatremia o Hyperkalemia o Acidosis o Pigmentation - Increased ACTH o Increased renin
Etiology o Autoimmune process o Tuberculosis o Histoplasmosis o Metastatic carcinoma o Amyloidosis o Bilateral adrenal hemorrhage o Inherited disorders - biosynthetic enzymes
Diagnosis o subnormal plasma levels of cortisol and aldosterone o reduced urinary excretion of 17-hydroxycorticoids
and aldosterone-18-glucuronide o ACTH increased o ACTH stimulation- subnormal response o Increased renin
Treatment o IV fluids and supportive care
o Glucocorticoid Life long hydrocortisone Double the dose during minor stress 10x usual dose for major stress IV
hydrocortisone o Minerelocorticoid
High sodium chloride intake is sufficient in most
Fludrocortisone in selected cases with special attention
o Medic alert bracelet
Adrenal cortical hyperfunction
Glucocorticoid: Cushing's syndrome o Hypothalamic-pituitary abnormality (Cushing's
disease) Adenoma - small to be recognized in most
o Ectopic ACTH level of cortisol very high rapid onset mostly presents as electrolyte and acid base
disturbance not enough time for overt manifestations of
Cushing's syndrome Small cell cancer, Carcinoid, Medullary
carcinoma Thyroid o Primary adrenal tumor (Carcinoma, Adenoma)
(ACTH independant) o Exogenous Glucocorticoid therapy (ACTH
independant) Minerelocorticoid: Disturbance in electrolyte and blood
pressure homeostasis o Adrenal tumors: (Adenoma, Carcinoma) o Bilateral adrenal hyperplasia
o Adrenal enzyme defects o Exogenous minerelocorticoids (Licorice,
Carbenoxolone) Clinical manifestations
o Obesity (centripedal, buffalo hump, supraclavicular fat pads, moon facies)
o Carbohydrate intolerance o Muscle wasting o Osteoporosis o Easy bruisability o Abdominal striae o Hypertension o Mood swings, depression, psychosis o Hirsutism, acne, menstrual disorders
Diagnosis o Typical clinical features o Excess of hormone
Random serum cortisol level 24 hour urinary excretion of 17-hyrdoxy-
cortisol o Dexamethasone suppression test
Plasma cortisol >5 mcg/dl suggests Cushing's syndrome
o High dose Dexamethasone suppression test ACTH dependant: Pituitary (Cushing's
disease): 50% or greater suppression ACTH independant: Ectopic ACTH and
Adrenal tumors: No suppression o ACTH levels
Normal to slightly high in Cushing's disease Very high in ectopic ACTH secretion by
tumors Undetectable levels in Adrenal tumors
o CRH stimulation test
o MRI, High resolution CT scan, Contrast enhanced CT scan of Pituitary or Adrenal gland
Normal pituitary fossa does not rule out adenoma
Treatment o Surgery (Pituitary or adrenal or ectpic tumor) o Radiation o Inhibition of adrenalcortical secretion: Mitotane
Hypothalamus Pituitary inter relations
Hypothalamus o Hypothalamic peptides stimulate secretion of anterior
pituitary hormones o Dopamine inhibits prolactin secretion o Under neural regulation by variety of
neurotransmitters o Regulated by closed -loop feedback system o TRH, GnRF, CRF, GRF are releasing hormones
Anterior pituitary o Adenohypophysis o Derived from Rathke's pouch o Somatomammotropins
Growth hormone Prolactin / lactogenic Chorionic somatomamotropin
o Corticotrophin (ACTH) Stimulate secretion of glucocorticoid by
adrenal cortex
o Pituitary glycoprotein hormones Thyroid stimulating hormone (TSH) Follicle stimulating hormone (FSH)
Regulate ovulation and secretion of steroid by ovary
Leuteinizing hormone (LH) Regulate ovulation and secretion of
steroid by ovary Posterior pituitary
o Neurohypophysis o Anatomical extension of hypothalamus o Derived from diencephalon o Located in sella tursica o In the base of brain
Tests of anterior pituitary function o ACTH
ACTH / undetectable in normal basal state Deficiency: Stimulation by induced
hypoglycemia / of hypothalamus CRF not available for clinical use Hypothalamic problem
Positive CRF test Negative response to
hypoglycemia Pituitary problem
Negative CRF test Negative response to
hypoglycemia ACTH excess
Suppression with dexamethasone o TSH
Deficiency: TRH stimulation: TSH levels increase up to 15
Pituitary problem: Flat response
Hypothalamic problem: Normal response
Excess Flat response to TRH
o Gonadotropins Deficiency GnRH stimulation Clomiphere stimulation
Hypothalamic dysfunction Normal response to GnRH
stimulation Response to Clomiphere
stimulation Pituitary dysfunction
Excess o Prolactin o Growth hormone
Measurable Deficiency: stimulation by hypoglycemia, L-
dopa, GRF Excess: Glucose loading
Anterior pituitary hypofunction
Hypothalamic defect Pituitary gland defect Common Etiology
o Tumors o Granulomas o Vascular necrosis o Surgery o Radiation o Compression by a space occupying lesion
Clinical features o Growth hormone
Short stature Delayed puberty
o ACTH Symptoms of adrenal cortical deficiency
o TSH Symptoms of hypothyroidism
o Gonadotropin Amenorrhea Diminished libido Loss of pubic and axillary hair Atrophy of breast and Testis
Diagnosis o Differentiate from polyglandular deficiency states o Deficiency of major target organ products o Absence of compensatory increases of tropic
hormones of pituitary o Establish abnormality in the hypothalamic-pituitary-
axis o Use of stimulation studies o Use of hypothalamic releasing factors to distinguish
between Hypothalamic and pituitary dysfunction Treatment
o Replacement of specific hormones Caution in thyroid replacement. Concomitant
or preceding replacement of glucocorticoids o Treat etiology
Anterior pituitary hyperfunction
Usually benign slow growing tumors o Neurological symptoms (Headache) o Visual defects (bitemporal hemianopsia) o Pituitary insufficiency o Excessive secretion of any of the anterior pituitary
hormones
Prolactin / Galactorrhea Growth hormone / Acromegaly, Gigantism (in
young) ACTH / Cushing's syndrome
o Diagnosis Clinical picture Excess of the hormone Inability to suppress by physiological
maneuvers MRI and high resolution CT for evaluation of
tumor o Treatment options
Correct deficiencies Surgery Radiation Bromocriptine
Disorders of posterior pituitary
Oxytocin / Release of breast milk, promote uterine contraction in labor
Anitdiuretic hormone (ADH) / Regulates water metabolism o Response to serum osmolality, hypovolemia and
hypotension o Normal serum osmolality 285 o Acts on distal nephron to induce an increased water
permeability o Excess: Water intoxication. Syndrome of
inappropriate ADH secretion o Deficiency: Diabetes insipidus
Central vs Nephrogenic Central : due to hypothalamic rather than
pituitary problem
AVP is stored in pituitary but synthesized in the hypothalamus
Polyuria (>3 L/day) and polydypsia Dilute urine (sp gr <1010 or osmolality <300) Need to distinguish from psychogenic
polydypsia Water deprivation test followed by pitressin
o Treatment Chlorpropamide ADH replacement by nasal insufflations
Hypothyroidism
List common symptoms of hypothyroidism.
Answer
Weakness Fatigue Memory impairment Cold intolerance Constipation Loss of hair Hoarseness Deafness Menstrual irregularity
What are the physical findings of a patient with hypothyroidism?
Answer
Dry coarse skin Periorbital edema Coarse thin skin Thick tongue Slow speech Deep voice Delayed Achilles' tendon reflex time Bradycardia
What are the common etiologies for primary hypothyroidism?
Answer
Primary hypothyroidism
Hashimotto's thyroiditis Idiopathic Post therapy for hyperthyroidism External beam radiotherapy Lithium, Amiodarone Iodide deficiency
What historical information will help you in identifying the etiology for primary hypothyroidism?
Answer
Hashimotto's thyroiditis o Family history or the presence in the patient of other
autoimmune endocrine disease
o Schmidt's syndrome / Hashimotto's and pernicious anemia and diabetes mellitus
Idiopathic Post therapy for hyperthyroidism
o Radioactive iodine therapy / History of radioactive iodine therapy
o Subtotal thyroidectomy / History of thyroidectomy External beam radiotherapy / history of neck radiation for
lymphoma or head and neck cancer Lithium, amiodarone Iodide deficiency / underdeveloped countries
How does physical examination of the thyroid gland help in the differential diagnosis of hypothyroidism?
Answer
Hashimotto's thyroiditis o enlarged thyroid
Idiopathic o atrophic thyroid
Post therapy for hyperthyroidism o depends on etiology
External beam radiotherapy o radiation changes over thyroid (pigmentation,
induration) Lithium, Amiodarone
o goiter Iodide deficiency
o goiter
What are the common etiologies for secondary hypothyroidism?
Answer
Hypothalamic dysfunction Pituitary dysfunction
What are the common etiologies for secondary hypothyroidism due to hypothalamic dysfunction?
Answer
Therapeutic irradiation Hypothalamic tumors
o germinoma o meningioma o hamartoma
What are the symptoms and signs that would alert you to the possibility of hypothalamic lesion?
Answer
Diabetes insipidus Narcolepsy Excessive appetite Marked anorexia Hyperthermia Marked hypothermia
What are the common etiologies for secondary hypothyroidism due to pituitary dysfunction?
Answer
Pituitary dysfunction /secondary adrenal insufficiency, hypogonadism, growth hormone deficiency
o Pituitary tumor o Post partum pituitary necrosis o Sarcoidosis o Metastatic carcinoma involving pituitary,
hypothalamus or stalk o Rathke's cleft cyst, craniopharyngioma, carotid artery
aneurysm compressing pituitary
What are the signs and symptoms that would suggest pituitary tumor?
Answer
Space-occupying mass of pituitary
Headache Bitemporal hemianopsia 3rd, 4th, or 6th nerve defects Seizures Rhinorrhea Meningitis
What would make you suspect postpartum pituitary necrosis as the etiology for pituitary dysfunction?
Answer
History of shock or massive hemorrhage at time of delivery
Inability to breast feed Amenorrhea afterwards
Which tests would help confirm the diagnosis of hypothyroidism?
Answer
Total T4: Low Free T4: Low TSH Free T3: of no value
Which lab test helps you to distinguish primary from secondary hypothyroidism?
Answer
TSH o increased / primary o decreased / secondary
Baseline and dynamic anterior pituitary hormone testing for deficiencies and overproduction
How do you distinguish hypothalamic from pituitary dysfunction as the etiology for secondary hypothyroidism?
Answer
TRH stimulation:
Primary: Exaggerated TSH response. TSH levels increase up to 15
Pituitary: Flat TSH response Hypothalamus: Normal TSH response
Which tests helpful in the diagnosis of identifying a pituitary mass?
Answer
MRI with gadolinium enhancement to document the presence of a mass
Testing for other tumor markers (alpha subunits)
What are the common non-specific lab abnormalities of hypothyroidism?
Answer
CPK Anemia Bradycardia, low voltage and non specific ST T wave
changes Hypoxia with hypercapnea
What are the treatment options for primary hypothyroidism?
Answer
Thyroid hormone replacement therapy with non-generic l-thyroxin or a generic form that has undergone rigorous quality controlled supervision of the manufacturing process.
With risk factors for coronary arterial disease, it would be wise to start with a low dose of thyroid hormone and increase the dose slowly.
What are the treatment options for secondary hypothyroidism?
Answer
Evaluate if secondary hypoadrenalism is present If preset, treat simultaneously with the treatment of the
hypothyroidism Also evaluate whether hypogonadism and/or growth
hormone deficiency is present and treat accordingly Then treat the cause of the secondary hypothyroidism
What are the components of total serum thyroxin?
Answer
Free thyroxine 0.03% Thyroxine binding albumin 10% Thyroxine binding prealbumin 20% Thyroxine binding globulin 70%
Alterations in these binding proteins can alter serum thyroxine values and mistaken diagnosis of hypo or hyperthyroidism can be made.
Describe euthyroid hypothyroxinemia / sick syndrome.
Answer
Clinical picture Normal sized thyroid gland Low serum TBG Hypoalbuminemia / nephrotic syndrome, cirrhosis Low serum total T4 Normal free T4 Normal TSH Normal TSH response to TRH
What is sub clinical hypothyroidism?
Answer
Euthyroid Normal serum T4 and T3 Elevated TSH
Hyperthyroidism
What are the symptoms of hyperthyroidism?
Answer
Symptoms: Potentiation of sympathetic system by excess thyroxine
Nervousness Heat intolerance Palpitations
Tremor Weight loss in spite of voracious appetite Weakness particularly proximal muscle group Hyper defecation
What are the physical findings of hyperthyroidism?
Answer
Thyroid enlargement o pyramidal lobe o bruit
Potentiation of sympathetic system by excess thyroxine o lid lag o warm moist skin o fine tremor o brisk reflexes o tachycardia
Onycholysis / Plumber's nails Mucopolysaccharide infiltration
o proptosis o ophthalmopathy: diplopia o pretibial myxedema o clubbing/ thyroid acropachy
What are the common etiologies for hyperthyroidism?
Answer
� Grave's disease
� Toxic multinodular goiter
� Toxic adenoma
� Factitious thyrotoxicosis
� Toxic struma ovari
� Thyroiditis
How does physical examination of the thyroid help in the differential diagnosis of hyperthyroidism?
Answer
� Graves disease
o diffuse enlargement
o bruit
� Toxic multinodular goiter
o multiple nodules
� Toxic adenoma
o single nodule
� Factitious thyrotoxicosis
o small thyroid
� Toxic struma ovari
o small thyroid
� Thyroiditis
o diffuse enlargement
What tests are useful to confirm hyperthyroidism?
Answer
Total T4: high Free T4: High Free T3: High TSH: Decreased
What are the tests useful to distinguish Grave's disease from other causes?
Answer
RAIU/ Scintiscan o increased uptake / symmetrical goiter / Graves o heterogynous uptake / asymmetric / thyroiditis,
multinodular goiter o hot nodule / toxic adenoma o decreased / factitious and struma ovari and
thyroiditis TRAb TSI
Thyroid auto antibodies are insensitive TRH stimulation: flat TSH response in Grave's disease
Describe the lab findings in a patient with euthyroid hyperthyroxinemia, related to alteration in TBG.
Answer
High serum TBG Estrogens hepatitis, 5-fluorouracil High serum total T4 Normal free T4 Normal TSH
Describe the clinical and lab findings in a patient with euthyroid hyperthyroxinemia, unrelated to TBG levels.
Answer
Clinical picture Acute non-thyroidal illness, psychiatric illness, drugs Normal sized thyroid gland High serum total T4 High free T4 Unrelated to TBG
What are the treatment options for hyperthyroidism?
Answer
Antithyroid drug therapy Radioactive iodine therapy
Surgery Symptomatic therapy with beta blockers
What are the treatment options based on the etiology?
Answer
Graves disease o Induce euthyroid state with antithyroid drug therapy
first o Radioactive iodine therapy
majority preferred form of treatment o Surgery
for children large goiter
Toxic multinodular goiter o Induce euthyroid state with antithyroid drug therapy
first o Radioactive iodine therapy
majority o Surgery �
large goiter pressure complications from goiter
Toxic adenoma o Radioactive iodine therapy or o Surgery
Thyroiditis / symptomatic therapy only Factitious thyrotoxicosis / treat the personality problem
How would you treat a pregnant patient with hyperthyroidism?
Answer
Treat with antithyroid drugs only Surgery is rarely indicated Radioactive iodine therapy should never be used Close monitoring of newborn for thyroid function